Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo

Riccioni, Teresa; Cirielli, Corrado; Wang, X; Passaniti, Antonino; Capogrossi, Maurizio C.

doi:10.1038/sj.gt.3300681

Cited by 50 publications

(29 citation statements)

References 25 publications

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“…These data suggest that in our model, p53 does not induce inhibition of angiogenesis, a mechanism known to be part of the p53-mediated tumor regression. 28,29 Then, the simplest hypothesis to explain our results is the daily death of a few percent of malignant cells as shown by necrosis observed in all samples. Then in the absence of cell proliferation, p53 expressing tumors progressively regress.…”

Section: Discussionmentioning

confidence: 84%

Cell cycle arrest is sufficient for p53-mediated tumor regression

et al. 2001

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Section: Discussionmentioning

confidence: 84%

Cell cycle arrest is sufficient for p53-mediated tumor regression

et al. 2001

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“…RAdp53 is a replication-defective recombinant adenovirus containing the cDNA for human wt p53 driven by the cytomegalovirus promoter and has been described previously. 25,26 RAdlacZ expresses lacZ 27 and RAdTIMP-2 expresses the human TIMP-2 gene from the CMVIEP. 28 RAdbcl2 and RAdcrmA contain the cDNA for bcl2 and crmA, respectively.…”

Section: Recombinant Adenovirusesmentioning

confidence: 99%

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis

et al. 2001

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Patency of autologous human saphenous vein coronary artery bypass grafts (CABG) is compromised by intimal thickening and superimposed atherosclerosis, caused by migration of vascular smooth muscle cells (SMC) to the intima where they proliferate. Here, using adenoviral transfer, we have targeted SMCs using wild-type p53 (wt p53) overexpression. Initial in vitro analyses demonstrated that wt p53 overexpression had no effect on SMC proliferation but promoted apoptosis, which was inhibited by co-expression of bcl2 or crmA. Wt p53 inhibited SMC invasion through reconstituted matrices, a phenotype not affected by bcl2 or crmA. Overexpression of wt p53 in human saphenous vein

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“…Unregulated expression of p21 CIP1 can lead to apoptosis (Smith, 2002). Ectopic overexpression of p53 by adenoviral delivery to EC also increased p21 CIP1 expression and interfered with EC differentiation (Riccioni et al, 1998). The c-myc proto-oncogene represses p21 CIP1 expression (Claassen and Hann, 2000) and Runx2 transgenic mice develop lymphomas in association with c-myc (Stewart et al, 1997;Vaillant et al, 1999), suggesting that RUNX2 may regulate downstream targets much like c-myc .…”

Section: Transcriptional Repression Of the P21 Cip1 Promotermentioning

confidence: 99%

Regulation of TGFβ1-mediated growth inhibition and apoptosis by RUNX2 isoforms in endothelial cells

et al. 2004

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Runx transcription factors regulate viral growth, hematopoiesis, bone formation, angiogenesis, and gastric epithelial development through specific DNA-binding motifs on target gene promoters. Vascular endothelial cells (ECs) express RUNX genes that are activated by angiogenic factors. The RUNX2 gene also activates the vascular endothelial growth factor promoter. Alternatively spliced forms of RUNX genes have been described, but their functions in angiogenesis have not been elucidated. In this study, expression of a novel alternatively spliced variant of RUNX2 (RUNX2D8), lacking the region encoded by exon 8, was detected in aortic tissue undergoing angiogenesis in vitro and in ECs. Expression of RUNX2 and RUNX2D8 increased in vascular sprouts concomitant with expression of cellular proteases and cytokines known to mediate angiogenesis. RUNX2 DNA-binding activity was expressed in proliferating but not quiescent ECs. Ectopic expression of RUNX2 in ECs increased cell sprouting, cell proliferation, DNA synthesis, and phosphorylation of phosphorylated retinoblastoma relative to control transfectants while RUNX2, but not RUNX2D8 transfectants, acquired resistance to growth inhibition by transforming growth factor (TGFb 1 ). Furthermore, RUNX2D8-transfected cells were more sensitive to TGFb 1 -induced apoptosis than RUNX2 transfectants. Consistent with these data, the RUNX2 gene was a strong repressor of the promoter of the cyclin-dependent kinase inhibitor, p21 CIP1 , while RUNX2D8 was a competitive inhibitor of RUNX2 and exhibited weak repression activity. These results support the hypothesis that ECs regulate growth and apoptosis, in part, by alternative splicing events in the RUNX2 transcription factor to affect the TGFb 1 signaling pathway. The exon 8 domain of RUNX2 may contribute to the strong repression activity of RUNX2 for some target gene promoters.

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Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo

Cited by 50 publications

References 25 publications

Cell cycle arrest is sufficient for p53-mediated tumor regression

Cell cycle arrest is sufficient for p53-mediated tumor regression

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis

Regulation of TGFβ1-mediated growth inhibition and apoptosis by RUNX2 isoforms in endothelial cells

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